In Search of an Ideal CAR-T Cell Antigen Target

Chimeric antigen receptor T (CAR-T) cells are proving their value in hematological cancers such as B cell acute lymphoid leukemia (B-ALL). This success is in great part due to the chosen target antigen, the lineage marker CD19, that is expressed by leukemia blasts and B lymphocytes, which are not crucial. For solid tumors, the challenge is greater because antigen expression is highly heterogeneous within the tumor and even an efficient CAR-T strategy would not kill all tumor cells. Also, many antigens are shared between solid tumors and healthy cells, causing off-target cell lysis and dangerous collateral damage. New antigen sources are emerging as targets, such as viruses, endogenous viruses, and immune checkpoint molecules. New technologies are in search of the ideal target, with antigen combinations the leading candidates.